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Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways

Litchi seeds have been traditionally used in Chinese herbal formula for urologic neoplasms including prostate cancer (PCa). However, the effective components of Litchi seeds and the mechanisms of their actions on PCa cell growth and metastasis remain unclear. In this study, we investigated the effec...

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Autores principales: Chang, Ming, Zhu, Dan, Chen, Yanjiang, Zhang, Weiquan, Liu, Xi, Li, Xiao-Lan, Cheng, Zhiping, Su, Zhiheng, Zhang, Jian, Lu, Yi, Guo, Hongwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495171/
https://www.ncbi.nlm.nih.gov/pubmed/34630125
http://dx.doi.org/10.3389/fphar.2021.758219
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author Chang, Ming
Zhu, Dan
Chen, Yanjiang
Zhang, Weiquan
Liu, Xi
Li, Xiao-Lan
Cheng, Zhiping
Su, Zhiheng
Zhang, Jian
Lu, Yi
Guo, Hongwei
author_facet Chang, Ming
Zhu, Dan
Chen, Yanjiang
Zhang, Weiquan
Liu, Xi
Li, Xiao-Lan
Cheng, Zhiping
Su, Zhiheng
Zhang, Jian
Lu, Yi
Guo, Hongwei
author_sort Chang, Ming
collection PubMed
description Litchi seeds have been traditionally used in Chinese herbal formula for urologic neoplasms including prostate cancer (PCa). However, the effective components of Litchi seeds and the mechanisms of their actions on PCa cell growth and metastasis remain unclear. In this study, we investigated the effects and molecular mechanisms of the Total Flavonoid of Litchi Seed (TFLS) in PCa PC3 and DU145 cell lines. We found that TFLS significantly inhibited the PCa cell proliferation, induced apoptosis, and prevented cell migration and invasion. Furthermore, we observed that TFLS upregulated the expression of epithelial biomarker E-cadherin and downregulated mesenchymal biomarker Vimentin. TFLS also increased the expression of cleaved-PRAP and Bax, and decreased the expression of Bcl-2 in both PC3 and DU145 cells. Besides, TFLS inhibited AKT signaling pathway by reducing the phosphorylation of AKT and activities of downstream signal transducers including mTOR, IκBα and NF-kB. Finally, TFLS treated mice exhibited a significant decrease in tumor size without toxicity in major organs in vivo. These results indicated that TFLS could suppress PCa cell growth in vivo and inhibit PCa cell proliferation and metastasis in vitro through induction of apoptosis and phenotypic reversal of EMT, which may be achieved by inhibiting the AKT/mTOR and NF-κB signaling pathways. Taken together, our data provide new insights into the role of TFLS as a novel potent anti-cancer agent for the treatment of PCa.
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spelling pubmed-84951712021-10-08 Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways Chang, Ming Zhu, Dan Chen, Yanjiang Zhang, Weiquan Liu, Xi Li, Xiao-Lan Cheng, Zhiping Su, Zhiheng Zhang, Jian Lu, Yi Guo, Hongwei Front Pharmacol Pharmacology Litchi seeds have been traditionally used in Chinese herbal formula for urologic neoplasms including prostate cancer (PCa). However, the effective components of Litchi seeds and the mechanisms of their actions on PCa cell growth and metastasis remain unclear. In this study, we investigated the effects and molecular mechanisms of the Total Flavonoid of Litchi Seed (TFLS) in PCa PC3 and DU145 cell lines. We found that TFLS significantly inhibited the PCa cell proliferation, induced apoptosis, and prevented cell migration and invasion. Furthermore, we observed that TFLS upregulated the expression of epithelial biomarker E-cadherin and downregulated mesenchymal biomarker Vimentin. TFLS also increased the expression of cleaved-PRAP and Bax, and decreased the expression of Bcl-2 in both PC3 and DU145 cells. Besides, TFLS inhibited AKT signaling pathway by reducing the phosphorylation of AKT and activities of downstream signal transducers including mTOR, IκBα and NF-kB. Finally, TFLS treated mice exhibited a significant decrease in tumor size without toxicity in major organs in vivo. These results indicated that TFLS could suppress PCa cell growth in vivo and inhibit PCa cell proliferation and metastasis in vitro through induction of apoptosis and phenotypic reversal of EMT, which may be achieved by inhibiting the AKT/mTOR and NF-κB signaling pathways. Taken together, our data provide new insights into the role of TFLS as a novel potent anti-cancer agent for the treatment of PCa. Frontiers Media S.A. 2021-09-23 /pmc/articles/PMC8495171/ /pubmed/34630125 http://dx.doi.org/10.3389/fphar.2021.758219 Text en Copyright © 2021 Chang, Zhu, Chen, Zhang, Liu, Li, Cheng, Su, Zhang, Lu and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chang, Ming
Zhu, Dan
Chen, Yanjiang
Zhang, Weiquan
Liu, Xi
Li, Xiao-Lan
Cheng, Zhiping
Su, Zhiheng
Zhang, Jian
Lu, Yi
Guo, Hongwei
Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways
title Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways
title_full Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways
title_fullStr Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways
title_full_unstemmed Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways
title_short Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways
title_sort total flavonoids of litchi seed attenuate prostate cancer progression via inhibiting akt/mtor and nf-kb signaling pathways
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495171/
https://www.ncbi.nlm.nih.gov/pubmed/34630125
http://dx.doi.org/10.3389/fphar.2021.758219
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